White Vastus Muscles Research Articles

Increased insulin sensitivity and insulin signaling protein content following regular exercise in T1‐diabetic rats

Type 1 diabetic (T1D) patients can develop insulin insensitivity due to the daily requirement of exogenous insulin. Regular exercise has been shown to improve insulin sensitivity (IS) through the increased expression of muscle Glut4 and insulin receptor (IR) content. This study examined the role of exercise on IS and Glut4 and IR expression in T1D rats. Thirty animals were randomly divided into 3 groups; control (C), diabetic sedentary (D), and diabetic exercised (DE). D and DE were injected with STZ and implanted with insulin pellets to maintain blood glucose levels between 9 and 15 mM. DE ran on a treadmill at 27m/min, 1hr/day, 5days/wk for 10wks. Compared to C, D demonstrate a significant decrease in Glut4 and IR protein content in the red (RV) and white (WV) vastus muscles (p<0.05), and a significant reduction in blood glucose clearance following an intravenous glucose challenge (p<0.05). DE demonstrated a significant increase in Glut4 protein in RV and WV (p<0.05), while IR protein content was elevated in the WV only (p<0.05). Also, blood glucose clearance rates were significantly increased in DE compared to D (p<0.05). To conclude, STZ-diabetic rodents exhibit insulin insensitivity which can be alleviated through regular exercise. These improvements in IS though exercise are concomitant with changes in Glut4 and IR protein content in a muscle-specific fashion. Supported by CIHR Grant #CCT- 83029.

Whole Body Deletion of AMP-activated Protein Kinase β2 Reduces Muscle AMPK Activity and Exercise Capacity

AMP-activated protein kinase (AMPK) β subunits (β1 and β2) provide scaffolds for binding α and γ subunits and contain a carbohydrate-binding module important for regulating enzyme activity. We generated C57Bl/6 mice with germline deletion of AMPK β2 (β2 KO) and examined AMPK expression and activity, exercise capacity, metabolic control during muscle contractions, aminoimidazole carboxamide ribonucleotide (AICAR) sensitivity, and susceptibility to obesity-induced insulin resistance. We find that β2 KO mice are viable and breed normally. β2 KO mice had a reduction in skeletal muscle AMPK α1 and α2 expression despite up-regulation of the β1 isoform. Heart AMPK α2 expression was also reduced but this did not affect resting AMPK α1 or α2 activities. AMPK α1 and α2 activities were not changed in liver, fat, or hypothalamus. AICAR-stimulated glucose uptake but not fatty acid oxidation was impaired in β2 KO mice. During treadmill running β2 KO mice had reduced maximal and endurance exercise capacity, which was associated with lower muscle and heart AMPK activity and reduced levels of muscle and liver glycogen. Reductions in exercise capacity of β2 KO mice were not due to lower muscle mitochondrial content or defects in contraction-stimulated glucose uptake or fatty acid oxidation. When challenged with a high-fat diet β2 KO mice gained more weight and were more susceptible to the development of hyperinsulinemia and glucose intolerance. In summary these data show that deletion of AMPK β2 reduces AMPK activity in skeletal muscle resulting in impaired exercise capacity and the worsening of diet-induced obesity and glucose intolerance.

Increased contractile acitivity induces autophagy in skeletal muscle

Contractile activity is essential in maintaining and promoting the oxidative phenotype of fatigue resistance, metabolic flexibility, insulin sensitivity and resistance to oxidative stress in skeletal muscle. This requires constant remodeling of structural proteins and organelles (e.g. mitochondria). We therefore hypothesized that autophagy, a catabolic process involved in the degradation of long‐lived proteins and organelles, is enhanced by increased contractile activity (i.e. endurance exercise). We submitted adult mice (12‐wk old, C57BL6) to 28 days of voluntary wheel running and used sedentary mice as controls (n=10/group). The expression of proteins associated with autophagosome formation (Beclin 1, LC3‐I+LC3‐II), mitochondrial autophagy (Bnip3), and aggregate protein degradation (p62/SQSTM1) were measured in the exercise‐recruited plantaris muscles. Consistent with our hypothesis, exercise training resulted in significant induction of Beclin1 (33%), Bnip3 (41.5%), LC3‐I+LC3‐II (43%) and LC3‐II‐to‐LC3‐I ratio (210%), and reduction of p62 (24%). The same directional changes were observed when tonic, oxidative soleus muscles were compared with phasic, glycolytic white vastus muscles in sedentary mice. Our findings suggest a role for autophagy in contractile activity‐mediated maintenance and promotion of oxidative phenotype in skeletal muscle.This study was funded by NIH Grant AR050429 (Zhen Yan).

Sympathetic modulation of baseline hindlimb blood flow and vascular conductance in a model of prediabetes using young Zucker Diabetic Fatty rats

Although associated with vascular disease, few studies have addressed the impact of prediabetes on vascular function. Thus, we sought to identify differences in baseline sympathetic vascular control between male Zucker (pre)Diabetic Fatty rats (PD) and lean controls (CTL) (n = 11/group). Hindlimb blood flow (Qh) and vascular conductance (VC) were assessed under local infusion of BIBP3226 (NPY Y1‐receptor (Y1R) antagonist), prazosin (α1‐receptor antagonist) and dual blockade. With no differences in baseline, BIBP3226 increased Qh 0.3 ± 0.1 ml/min in both groups and VC increased 4.2 ± 0.9 and 4.5 ± 1.1 μl/min/mmHg in PD and CTL respectively (P &lt; 0.05). Prazosin increased Qh 0.2 ± 0.04 and 0.2 ± 0.1 ml/min and VC increased 3.3 ± 0.5 and 4.2 ± 1.0 μl/min/mmHg in PD and CTL respectively (P &lt; 0.05). Dual blockade increased Qh 0.2 ± 0.05 ml/min in both groups and VC increased 4.6 ± 1.2 and 4.4 ± 0.72 μl/min/mmHg in PD and CTL respectively (P &lt; 0.05). Recovery time from maximum after drug infusion to 37% of baseline (1/e) for Qh and VC was shorter in PD vs. CTL (% of CTL, Qh and VC respectively: BIBP3226 68% and 53%, Prazosin 75% and 81%, dual blockade 78% and 70%) (P &lt; 0.05). In support, red and white vastus muscle Y1R, α1R, and tyrosine hydroxylase expression was higher in PD vs. CTL (P &lt; 0.05). These data suggest that the SNS is upregulated in prediabetes leading to persisting effects on skeletal muscle blood flow. NSERC and NIH.

Estrogen modulates the contribution of neuropeptide Y to baseline hindlimb blood flow control in female Sprague-Dawley rats

The purpose of this study was to determine the role of estrogen in neuropeptide Y (NPY) and Y(1) receptor (Y(1)R)-mediated vascular responses in female rats. Based on earlier work from our laboratory that female rats lacked an NPY contribution to hindlimb vascular conductance relative to males, we tested the hypothesis that estrogen modulates Y(1)R-mediated hindlimb blood flow control. Thus it was expected that ovariectomy would: 1) increase skeletal muscle Y(1)R expression, 2) decrease skeletal muscle Y(2) receptor (Y(2)R) expression, 3) decrease peptidase activity, and/or 4) increase overall skeletal muscle NPY concentration. Separate groups of control (CTL), ovariectomized (OVX), and OVX + 17beta-estradiol replacement (OVX + E(2); 21-day pellet) rats were studied. Animals were anesthetized and given localized hindlimb delivery of BIBP-3226 (Y(1)R antagonist), while femoral artery blood flow and blood pressure were recorded. Tissue samples from the white and red vastus lateralis muscle were extracted to examine Y(1)R and Y(2)R expression, peptidase activity, and NPY concentration. We found that Y(1)R blockade resulted in increased baseline hindlimb blood flow and vascular conductance in OVX rats, whereas no change was noted in CTL or OVX + E(2) groups (P < 0.05). This enhanced functional effect in the OVX group aligned with greater skeletal muscle Y(1)R expression in white vastus muscle and a substantial increase in NPY concentration in both white and red vastus muscle compared with CTL and OVX + E(2) groups. There was no change in Y(2)R expression or peptidase activity among the groups. These data support the hypothesis that estrogen blunts Y(1)R activation in the rat hindlimb through an effect on Y(1)R expression and NPY concentration.

Oestrogen receptor‐alpha activation augments post‐exercise myoblast proliferation

Our laboratory has shown that oestrogen acts to augment myoblast (satellite cell) activation, proliferation and total number and that this may occur through an oestrogen receptor (OR)-mediated mechanism. The purpose of this study was to further investigate the mechanism of oestrogen influence on augmentation of post-exercise myoblast numbers through use of a specific OR-alpha agonist, propyl pyrazole triol (PPT). Ovariectomized rats were used (n = 64) and separated into four groups: sham, oestrogen supplemented, agonist supplemented, and a combined oestrogen and agonist supplemented group. These groups were further subdivided into control (unexercised) and exercise groups. Surgical removal of white vastus and soleus muscles was performed 72 h post-exercise. Muscle samples were immunostained for the myoblast markers Pax7 and MyoD. A significant increase in total (Pax7-positive) and activated (MyoD-positive) myoblasts was found in all groups post-exercise. A further significant augmentation of total and activated myoblasts occurred in oestrogen supplemented, agonist supplemented and the combined oestrogen and agonist supplemented groups post-exercise in white vastus and soleus muscles relative to unsupplemented animals. These results demonstrate that both oestrogen and the specific OR-alpha receptor agonist, PPT, can significantly and to similar degrees augment myoblast number and activation following exercise-induced muscle damage. This suggests that oestrogen acts through an OR-mediated mechanism to stimulate myoblast proliferation following exercise, with OR-alpha playing a primary role.

Oestrogen receptors mediate oestrogen‐induced increases in post‐exercise rat skeletal muscle satellite cells

Our laboratory recently demonstrated that increases in post-exercise muscle satellite cell numbers are augmented by oestrogen. We investigated whether muscle oestrogen receptors (ORs) mediate this effect through administration of an OR antagonist, ICI 182,780. Ovariectomized female rats were divided into three groups: sham, oestrogen (0.25 mg pellet) and oestrogen plus OR blocker (ICI 182,780). Each group was divided into control and exercised groups. ICI 182,780 (5 mg kg(-1) sc) was administered 1 day prior to and 6 days following oestrogen pellet implantation. After 8 days of oestrogen exposure, animals ran downhill for 90 min (17 m min(-1), -13.5 degrees grade) on a treadmill. Soleus and white vastus muscles were removed 24 and 72 h post-exercise and immunostained for total (Pax7), activated (MyoD) and proliferating (BrdU) satellite cells. Muscle damage was indirectly assessed by measuring beta-glucuronidase activity. Two markers (His48 and ED1) of leucocyte infiltration were also examined. beta-Glucuronidase activities and His48+ and ED1+ leucocytes increased post-exercise, and these increases were attenuated with oestrogen. ICI 182,780 did not influence the attenuating effect of oestrogen on leucocyte infiltration or beta-glucuronidase activities in muscle. Total (Pax7+), activated (MyoD+) and proliferating (BrdU+) satellite cells increased post-exercise, and these increases were augmented with oestrogen. Interestingly, ICI 182,780 abolished both exercise- and oestrogen-mediated increases in these satellite cell markers. Oestrogen may augment increases in muscle satellite cells following exercise through OR-mediated mechanisms; furthermore, the attenuation of post-exercise muscle damage and leucocyte infiltration by oestrogen appears to be a non-OR-mediated process.

Estrogen Attenuation of Post‐Exercise Muscle Leukocyte Infiltration is not Receptor Mediated

Previous work from our laboratory has demonstrated that estrogen will attenuate leukocyte infiltration into skeletal muscle following eccentric exercise. However the mechanisms by which estrogen exerts its effects are still uncertain. We investigated the role of estrogen receptors (ER) on muscle leukocyte infiltration following eccentric exercise through administration of the ER antagonist ICI 182,780 following downhill running to ovariectomized female rats with (E+) or without (E−) estrogen supplementation. At 24 and 48 h post‐exercise, soleus and white vastus muscles were removed and immunostained for HIS 48 (neutrophil) and ED1 (macrophage) positive cells. The increase in number of fibres positive for HIS 48 in soleus and positive for ED1 in the soleus and white vastus was significantly attenuated (p&lt;0.05) in E+ relative to E− rats at 24 hours post‐exercise. E+ rats administered the ER agonist also had significantly (p&lt;0.05) attenuated 24 h post‐exercise increases in HIS 48 and ED1 positive soleus and white vastus muscle fibres similar (p&gt;0.05) to those without ER antagonist. This suggests that the ability of estrogen to attenuate post‐exercise leukocyte infiltration into skeletal muscle is not ER‐mediated.Supported by NSERC Canada

Estrogen influences satellite cell activation and proliferation following downhill running in rats

To investigate the influence of estrogen on postexercise muscle repair processes, we examined the effects of estrogen supplementation (0.25-mg pellet) on numbers of myofibers positive for markers of total, activated, and proliferating satellite cells in rat skeletal muscles 72 h following downhill running. Ovariectomized female rats (n = 44) were divided into four groups (n = 11 per group): sham (no estrogen) controls (SC); sham, exercised (SE); estrogen-supplemented controls (EC); and estrogen-supplemented, exercised (EE). After 8 days of estrogen exposure, animals were exposed to 90 min of treadmill running at 17 m/min (-13.5 degrees ). Seventy-two hours later, soleus and white vastus muscles were removed and immunostained for total [paired box homeotic gene 7 (Pax7)], [activated myogenic differentiation factor D (MyoD)], and proliferating [5-bromo-2'-deoxyuridine (BrdU)] satellite cells. beta-Glucuronidase activity was increased (P < 0.05) in both muscles following exercise; however, the postexercise elevations in enzyme activity were attenuated in the EE group compared with the SE group in the soleus (P < 0.05). Immunohistochemical analysis revealed that exercised groups displayed increased numbers of myofibers containing total, activated, and proliferating satellite cells compared with control groups (P < 0.05). Furthermore, greater numbers of fibers positive for markers of total, activated, and proliferating satellite cells were observed postexercise in EE animals compared with SE animals for both muscles (P < 0.05). The results demonstrate that estrogen may potentially influence post-damage repair of skeletal muscle through activation of satellite cells.

Manipulating training intensity and volume in already well-trained rats: effect on skeletal muscle oxidative and glycolytic enzymes and buffering capacity

Well-trained endurance athletes undergo periods of high-intensity interval training (HIT) or high-volume training (HVT) to improve exercise performance, but little is known about the mechanistic changes that occur during this time. The purpose of this study was to examine the influence of HIT and HVT on the activities of citrate synthase (CS) and phosphofructokinase (PFK), and on intramuscular buffering capacity (betam) in already well-trained rats. At 4 weeks of age, Wistar rats were divided into sedentary (SED; n=18) and exercise training groups (n=38). Following a 10 week preliminary training program, trained rats were divided randomly into 3 further groups that completed 4 additional weeks of continued endurance (CON, n=14), high-intensity training (HIT, n=12), or high-volume training (HVT, n=12). Soleus (SOL), red and white gastrocnemius (RG and WG), and red and white vastus (RV and WV) muscles were removed 24-48 h after a final run-to-fatigue performance test (30 m.min(-1) 25% grade) to determine the activities of CS, PFK, and betam. No differences in run time to exhaustion were found between the groups. However the HIT group possessed CS and PFK activities and betam in WV muscle that were 60%, 24%, and 10% higher, respectively (all p<0.05), compared with the HVT group; differences were not found between the HIT and CON groups. Although no differences in run performance were found, HIT compared with HVT in already well-trained rats resulted in significantly higher oxidative and glycolytic capacities of fast-contracting fibres. No differences were shown in fast-contracting muscle between HIT and CON.

Estrogen Influence On Myogenic Satellite Cells Following Downhill Running In Male Rats

This study examined the effect of estrogen supplementation in rats on myogenic satellite cell quantities in type I and type II muscles following eccentric exercise. Gonad intact adult male rats divided into four groups, estrogen supplemented (25 mg estrogen pellet) control (EC), estrogen supplemented, exercised (EE), sham (no estrogen) control (SC) and sham, exercised (SE). After 1 wk of estrogen exposure the EE and SE animals performed 90 min of intermittent (5 min running/2 minrest) downhill running (−13.5° incline, 17 m/min). 72 hr later exercised (EE and SE) and control (EC and SC) animals were sacrificed and blood samples and soleus and white (superficial) vastus muscles surgically removed. Histochemical sections of soleus and white vastus muscles were examined for myogenic satellite cell content by use of Pax7 antibody and for neutrophil content by use of hematoxylin and eosin (H and E) staining procedures. Downhill running resulted in significant elevations in satellite cells and neutrophils detected in both soleus and white vastus muscle samples (P < 0.01). Interestingly, estrogen supplementation resulted in significantly greater (P < 0.01) post-exercise elevations in satellite cells detected in both soleus and white vastus muscle samples compared to sham (no estrogen) rats. Increases in neutrophils were significantly (P < 0.05) attenuated in estrogen supplemented rats relative to sham in soleus but not in white vastus muscles. Hence, estrogen supplementation in male rats accentuated the 72 hr post-downhill running increase in Pax7 detected myogenic satellite cell number in both soleus and white vastus muscles relative to unsupplemented rats. The mechanisms and physiological consequences of this effect are yet to be determined.

Oestrogen influence on myogenic satellite cells following downhill running in male rats: a preliminary study

This study examined the effect of oestrogen supplementation in rats on myogenic satellite cell quantities in type I and II muscles following eccentric exercise. Gonad intact adult male rats divided into four groups, oestrogen supplemented (25 mg oestrogen pellet) control (EC), oestrogen supplemented, exercised (EE), sham (no oestrogen) control (SC) and sham, exercised (SE). After 1 week of oestrogen exposure the EE and SE animals performed 90 min of intermittent downhill running (5 min running/2 min rest @-13.5 degrees incline and 17 m min(-1) speed). Seventy-two hours later exercised (EE and SE) and control (EC and SC) animals were killed and blood samples taken and soleus and white (superficial) vastus muscles surgically removed. Histochemical sections of soleus and white vastus muscles were examined for myogenic satellite cell content by use of Pax7 antibody and for neutrophil content by use of haematoxylin and eosin (H and E) staining procedures. Downhill running resulted in significant elevations in satellite cells and neutrophils detected in both soleus and white vastus muscle samples (P < 0.01). Interestingly, oestrogen supplementation resulted in significantly greater (P < 0.01) post-exercise elevations in satellite cells detected in both soleus and white vastus muscle samples compared with sham (no oestrogen) rats. Increases in neutrophils were significantly (P < 0.05) attenuated in oestrogen supplemented rats relative to sham in soleus but not in white vastus muscles. Oestrogen supplementation in male rats may have accentuated the 72 h post-downhill running increase in Pax7 detected myogenic satellite cell number in both soleus and white vastus muscles relative to unsupplemented rats. The mechanisms and physiological consequences of this effect are yet to be determined.

Changes of time course of sarcoplasmic reticulum CA2+ uptake and release in red and white vastus muscles after eccentric exercise

Changes of time course of sarcoplasmic reticulum CA2+ uptake and release in red and white vastus muscles after eccentric exercise

Estrogen attenuates HSP 72 expression in acutely exercised male rodents.

Estrogen has been shown to reduce post-exercise skeletal muscle damage. Exercise-induced muscle damage may be a factor in the elevated post-exercise expression of heat-shock proteins (HSPs). Thus, the present investigation was conducted in order to examine the influence of estrogen on post-exercise levels of HSP 72 and heat-shock cognate, HSC 73, in male and female rodents. Prior to an acute bout of treadmill running, male and female Sprague-Dawley rats received daily injections of either 40 microg x kg(-1) of beta-estradiol 3-benzoate or olive oil vehicle for 2 weeks. A two- to fourfold reduction in post-exercise HSP 72 content was observed in the heart, liver, lung and red and white vastus muscles of estradiol-treated males compared with their vehicle-injected counterparts (P < 0.05). Compared to the males, the females had significantly lower post-exercise HSP 72 levels which were not affected by estradiol supplementation. Moreover, estradiol administration in male rodents resulted in a HSP response similar to that of females following exercise. Thus, the results of the present investigation suggest that estrogen is the factor responsible for the observed differences in post-exercise HSP 72 levels between males and females.

Cocaine and exercise: alteration in carbohydrate metabolism in adrenodemedullated rats.

The combined treatment of cocaine-exercise (CE) causes an exaggerated catecholamine response, a rapid depletion of muscle glycogen, and accumulation of lactic acid. To assess the contribution of the adrenal medulla in the catecholamine response and to determine the role of epinephrine (Epi) on carbohydrate metabolism, cocaine (20 mg/kg ip) or saline was injected into sham-operated (Sham) or adrenodemedullated (AdM) rats, which then ran for 5 min at 56 m/min, 0% grade. In Sham rats, CE caused plasma Epi values (means +/- SE) to rise to 27.7 +/- 6.9 nM compared with 13.3 +/- 1.5 nM in saline-exercise (SE) and 0.8 +/- 0.2 nM in both AdM-CE and AdM-SE animals (P < 0.05). With minimal Epi in AdM, CE still caused glycogen to fall to lower levels (25.4 +/- 3.0 mumol/g vs. 40.5 +/- 2.4 mumol/g) and lactate to rise to higher levels (17 +/- 3 vs. 9 +/- 1 mumol/kg) in white vastus muscle than in SE group (P < 0.05). CE had no significant effect on soleus and red vastus glycogenolysis but it did cause lactate accumulation in red vastus. As a result, plasma lactate levels were also higher after CE compared with SE in AdM (17.9 +/- 2.0 vs. 8.5 +/- 0.5 mM, P < 0.05). We conclude that during CE 1) Epi is not essential to the alteration in carbohydrate metabolism; 2) the latter may be related to the other catecholamines; 3) the adrenal medulla is the only source of Epi; and 4) the adrenal medulla is not the source of the increased levels of norepinephrine or dopamine.

Cocaine and exercise

To compare the physiological response to a cocaine-exercise challenge in cocaine-conditioned animals with that of acute-cocaine animals, rats were injected i.p. with either cocaine (20 mg.kg-1) or saline, twice daily for 14 consecutive days. On the 15th day (test day) cocaine-conditioned rats received an i.v. injection of cocaine (5 mg.kg-1) (chronic group). One-half of the chronic saline rats also received the cocaine injection (acute group), while the other half received saline (saline group). Immediately after injection, all rats were either rested or exercised (22 m.min-1, 10% grade) for 30 min. For most parameters there was no difference between the responses of the chronic and acute cocaine groups at rest or to the cocaine-exercise challenge. During exercise, both cocaine groups had similarly higher lactate values than the saline animals (P < 0.05). Both groups had similarly greater reductions in glycogen content of the white and red vastus muscles than occurred in the saline group; and both groups had similar increases in corticosterone. In contrast, cocaine-conditioned animals had a greater rise in norepinephrine (P < 0.059) and epinephrine (P < 0.001) in response to cocaine-exercise than did the acute group. The mechanism responsible for the exaggerated catecholamine response in the chronic cocaine animals is unknown.

Effects of estradiol on lipoprotein lipase activity and lipid availability in exercised male rats.

The effects of 17 beta-estradiol 3-benzoate (10 micrograms.0.1 ml sunflower oil-1 x 100 g body wt-1) and exercise on tissue lipid content and lipoprotein lipase (LPL) activity were determined in male rats. Estradiol administration significantly (P < 0.05) increased fatty acid contents of resting adipose, plasma, and white and red vastus muscle tissues and red vastus muscle triacylglycerol. Adipose and plasma fatty acids and red and white vastus muscle triacylglycerol were significantly higher in exercised estradiol-administered animals than in exercised oil-administered animals. Estradiol administration significantly reduced resting adipocyte LPL activity by 71% and increased myocardial LPL activity by 96%. After exercise, red vastus LPL activity was significantly increased by 76% in estradiol-administered animals compared with oil-administered animals. Ratios of red vastus to adipose LPL activity and myocardial to adipose LPL activity at rest and after exercise were significantly greater in estradiol-administered than in oil-administered animals. Estradiol administration significantly increased the ratio of white vastus to adipose LPL activity of exercised animals. These data indicate that estradiol increases the availability of lipid substrate to exercising muscle from multiple sources, including adipose, plasma, and intracellular muscle triacylglycerol. The absolute increases in muscle LPL activity, combined with a greater ratio of muscle to adipose LPL activity, lead to increased distribution of plasma triacylglycerol-derived fatty acids toward muscle.

Effects of cocaine on glycogen metabolism and endurance during high intensity exercise.

Because cocaine causes a rapid sympathetic response and central euphoria, we tested whether it would improve endurance or alter carbohydrate metabolism during high-intensity activity. Thirty male rats (10 animals/group) were injected intraperitoneally with either saline (S) or one of two doses of cocaine-HCl (12.5 (C-1) or 20.0 (C-2) mg.kg-1 b.w.). Ten minutes later they began gradually running on a rodent treadmill. Within 2 min they were running at 56 m.min-1 until fatigued. The run time to exhaustion (mean +/- SE) for C-2 (569 +/- 97 s) was less than S (859 +/- 71) and C-1 (923 +/- 65) (P < 0.05) and 25% shorter (marginally insignificant) than a pretreatment run (754 +/- 67 s) (P > 0.05). Plasma lactate concentrations at exhaustion were 4.0 +/- 0.5 (S), 7.3 +/- 1.1 (C-1), and 13.9 +/- 2.5 (C-2) mmol (P < 0.05, S vs C-2). Lactate concentrations in white vastus muscle were also elevated by C (4.7 +/- 0.6 (S), 8.1 +/- 1.3 (C-1), and 15.0 +/- 3.7 (C-2) mumol.g-1, (P < 0.05, S vs C-2)], which correlated with the reduction in glycogen content in both C groups (9.9 +/- 2.3 (C-2), 10.3 +/- 1.2 (C-1), vs 33.9 +/- 2.0 (S) mumol.g-1]. These results show that, in spite of its purported stimulatory effect, cocaine treatment (20 mg.kg-1) immediately prior to intense exercise causes accelerated glycogen degradation and lactate accumulation in white vastus muscle during exercise and premature fatigue.

Metabolic adaptation to daily exercise of moderate intensity to exhaustion in the rat.

The rats were made to run daily to exhaustion, for 28 days at a speed of 1,200 m.h-1 on a treadmill set at a gradient of +10 degrees. The training increased the time of running to exhaustion [184 (SD 49) and 308 (SD 28) min on the 1st and 28th day, respectively; P < 0.001]. The body mass was reduced by training [257 (SD 21) g before and 221 (SD 20) g after; P < 0.001] whereas the food intake increased [9 (SD 1) g.100 g-1 body mass before and 14 (SD 2) g after; P < 0.001]. The heart mass was not affected by training. Training increased the resting glycogen concentration in muscles composed of different fibre types (soleus, white and red vastus muscles) and in the liver, but had no effect on its concentration in the heart and diaphragm. During exercise lasting for 30 min glycogen mobilization in the red vastus and soleus muscles and the liver was more pronounced after than before training. A "sparing" effect of training on the skeletal muscles and liver glycogen was markedly apparent only after exercise to exhaustion. The trained rats, contrary to the untrained, did not develop hypoglycaemia during exercise to exhaustion. An increase in the plasma free fatty acid concentration during exercise after training was delayed and attenuated compared to that before training. The 24-h excretion of urea after exercise to exhaustion on the 28th day of training was higher than on the 1st day by 39% (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of estradiol on tissue glycogen metabolism and lipid availability in exercised male rats

The effect of 17 beta-estradiol 3-benzoate (10 micrograms.0.1 ml sunflower oil-1.100 g body wt-1) on exercise performance, tissue glycogen utilization, and lipid availability was determined in male rats. In experiment 1, estradiol or oil was administered 1 h or 1-6 days before a treadmill run to exhaustion. No differences in body weight between oil- and estradiol-administered animals were observed during the 6-day treatment. Animals receiving estradiol for 3-6 days ran significantly longer and completed more work than oil-administered animals. Significant degradation of red and white vastus muscle, myocardial, and liver glycogen was observed in all animals run to exhaustion. In experiment 2, animals were administered estradiol for 5 days and then run for 2 h. The submaximal run for 2 h significantly reduced tissue glycogen content in red and white vastus muscle, heart, and liver of oil-administered animals. The latter effect was attenuated in both vastus muscles, liver, and myocardial tissues in the estradiol-administered animals. Estradiol administration significantly increased plasma fatty acids and lowered plasma lactate during the submaximal run. These data indicate that when body weight remained constant between groups of male rats, estradiol administration for 3-6 days increased exercise performance. Furthermore, estradiol administration for 5 days resulted in greater lipid availability and less tissue glycogen utilization during submaximal running for 2 h.